Although the methylnitrosourea (MNU)-induced mammary cancer model has been used extensively in studies related to chemoprevention and nutrition, few studies have been performed to characterize this experimental model of human breast cancer. The current data on the MNU model suggest that it is superior to the dimethylbenz(a)anthracene(DMBA) model with respect to the highly aggressive nature of the cancers and the greater sensitivity of the cancers to estrogens. Also, since MNU does not require metabolic activation, the model is ideal for determining the role that metabolic differences (such as those occurring invarious strains of rats, in animals during hormone treatment, etc.) play in the induction of mammary cancer by chemicals. Under our current grant, we have used this model to show that the decrease in susceptibility of the mammary gland in aging rats to chemical carcinogens is primarily due to changes occuring within the mammary gland and not to metabolic alterations. The studies described in this proposal are designed to further characterize the MNU-mammary model with respect to influence of hormones on cancer induction and to use this model to better define the importance of mammary gland morphology at the time of carcinogen treatment on mammary carcinogenesis. Specifically, studies are proposed to determine the effect of the stage of the estrus cycle and of progesterone on MNU cancer induction in Sprague-Dawley rats and to correlate the degree of mammary gland differentiation in various strains of rats at the time of carcinogen treatment to subsequent cancer incidence. Since previous studies have shown that pharmacological doses of estrogen plus progesterone given after carcinogen treatment can greatly alter mammary carcinogenesis, we also propose to determine whether pretreatment for a short period of time with the steroids might inhibit cancer initiation. We feel that if mammary gland changes can be induced with hormones in young animals prior to and during the period of high carcinogen susceptibility, a means of prevention of mammary cancer would be available.